Alternative titles; symbols
HGNC Approved Gene Symbol: COLEC11
Cytogenetic location: 2p25.3 Genomic coordinates (GRCh38): 2:3,595,112-3,644,644 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 2p25.3 | 3MC syndrome 2 | 265050 | Autosomal recessive | 3 |
COLEC11 is a member of the collectin family of C-type lectins, which contain a collagen-like domain and a carbohydrate recognition domain, and play a role in host-defense (Keshi et al., 2006).
By EST database screening using the carbohydrate recognition domain (CRD) of human liver collectin, CLL1 (COLEC10; 607620), followed by 5-prime RACE of human kidney cDNA libraries, Keshi et al. (2006) cloned COLEC11, which they called CLK1. The deduced 271-amino acid COLEC11 protein contains an N-terminal region with a cysteine residue, a collagen-like sequence, a neck region, a CRD, and a predicted signal peptide of 25-amino acids; the mature predicted protein consists of 246 amino acids. By RT-PCR analysis, Keshi et al. (2006) isolated putative splice variants for transcripts lacking exon 2, exon 3, and both exons 2 and 3. RT-PCR analysis detected COLEC11 transcripts in most tissues examined, with high expression in kidney, liver, fetal liver, small intestine, thymus, spinal cord, placenta, adrenal gland, pancreas, and several cell lines. No expression was detected in skeletal muscle, bone marrow, or in the human embryonic kidney cell line HEK293. Keshi et al. (2006) localized COLEC11 to the Golgi-endoplasmic reticulum (ER). Western analysis determined that COLEC11 is a secreted protein, and that all COLEC11 isoforms have oligomeric structures created through disulfide bonding. Keshi et al. (2006) detected native COLEC11 protein in human serum.
Rooryck et al. (2011) observed broadly distributed expression of Clk1 in mouse tissues at embryonic day (E) 13.5, including craniofacial cartilage, (nasal septum, Meckel cartilage, and posterior palate), heart, bronchi, kidney, and vertebral bodies. They also observed expression in palatal structures at E13.5 and E15.5. Examination of zebrafish embryos revealed colec11 expression in the pronephric duct, lateral hindbrain, and liver.
Using recombinant COLEC11, Keshi et al. (2006) showed that COLEC11 displays Ca(2+)-dependent binding to fucose, weaker binding to mannose, and does not bind N-acetyl-galactosamine, N-acetyl-glucosamine, or glucose. COLEC11 binds a variety of microbial saccharides including LPS from E. coli and Klebsiella pneumoniae, as well as S. cerevisiae mannan.
Rooryck et al. (2011) evaluated cellular localization of Clk1 in a murine chondrocyte cell line and observed specific localization in the Golgi apparatus, consistent with a secreted peptide. Using antisense morpholinos against the initiation site and the exon 2/intron 2 splice site in zebrafish embryos, Rooryck et al. (2011) found that the effect was dose-dependent, with higher doses producing heart edema, pronephric cyst formation, curved body axis, disorganized pigment distribution, and high mortality. Staining of cartilage in zebrafish morphants at 5 days postfertilization revealed reduced mandibular length, malformation of the anterior neurocranium with shortening of the trabeculae and ethmoid plate, and shortening and abnormal angulation of the ceratohyal cartilage compared to controls. Rooryck et al. (2011) tested for epistasis between COLEC11 and MASP1 (600521) by injection of suboptimal doses (below which no phenotype is seen when injected alone) of both colec11 and masp1 morpholinos into single-cell-stage zebrafish embryos, and found that approximately 73% developed severe craniofacial abnormalities and some developed clefts in the ethmoid plate. These results suggested that the COLEC11 and MASP1 gene products function in the same pathway.
In 4 consanguineous families with 3MC syndrome mapping to chromosome 2p25 (3MC2; 265050), Rooryck et al. (2011) analyzed candidate genes and identified homozygosity for 1 nonsense and 2 missense mutations and 1 in-frame deletion in the COLEC11 gene (612502.0001-612502.0004, respectively). Analysis of COLEC11 in additional 3MC patients revealed homozygous mutations in 3 more probands (see, e.g., 612502.0005 and 612502.0006).
In a brother and sister from a consanguineous Tunisian family with 3MC syndrome-2 (3MC2; 265050), Rooryck et al. (2011) identified homozygosity for a 496T-C transition in exon 8 of the COLEC11 gene, resulting in a ser169-to-pro (S169P) substitution at a conserved residue. The mutated alleles segregated with the disorder in the family and the mutation was not found in 60 Tunisian or 284 northern European control chromosomes.
In a sister and brother from a consanguineous Bangladeshi family with 3MC syndrome-2 (3MC2; 265050), Rooryck et al. (2011) identified homozygosity for a 1-bp deletion (45delC) in exon 2 of the COLEC11 gene, causing a frameshift predicted to result in premature termination. The mutated alleles segregated with the disorder in the family and the mutation was not found in 94 Bangladeshi or 284 northern European control chromosomes.
In 2 brothers from a consanguineous Afghan family with 3MC syndrome-2 (3MC2; 265050), Rooryck et al. (2011) identified homozygosity for a 610G-A transition in exon 8 of the COLEC11 gene, resulting in a gly204-to-ser (G204S) substitution at a highly conserved residue in the carbohydrate recognition domain. The G204S mutation was also detected in homozygosity in a Pakistani 3MC patient. The mutated alleles segregated with the disorder in both families and the mutation was not found in 72 Bangladeshi or 284 northern European control chromosomes. Using protein blotting, Rooryck et al. (2011) did not detect any secreted CLK1 in serum from the 2 affected Afghan brothers, in contrast to control samples, suggesting that the G204S substitution leads to cellular retention of the protein.
In a Saudi Arabian patient with 3MC syndrome-2 (265050), Rooryck et al. (2011) identified homozygosity for a 3-bp in-frame deletion (648CTC) in exon 8 of the COLEC11 gene, resulting in the deletion of a highly conserved serine residue (ser217del) in the carbohydrate recognition domain. The mutated alleles segregated with the disorder in the family, and the mutation was not found in 192 Saudi control chromosomes.
In a female patient with 3MC syndrome-2 (265050) from the Italian family originally reported by Mingarelli et al. (1996), Rooryck et al. (2011) identified homozygosity for a 1-bp deletion (300delT) in exon 6 of the COLEC11 gene, causing a frameshift predicted to result in premature termination within the neck domain. The mutated alleles segregated with the disorder in the family, and the mutation was not found in 334 northern European control chromosomes.
In a male patient with 3MC syndrome-2 (265050) from the Italian family originally reported by Carnevale et al. (1989), Rooryck et al. (2011) identified homozygosity for a 27-kb deletion encompassing exons 1 to 3 of the COLEC11 gene, predicted to result in complete loss of the N terminus and partial loss of the collagen-like domains of the protein. Sequence analysis of the proximal and distal breakpoints of the junction fragment revealed low copy repeat sequences (LCRs) corresponding to long interspersed nuclear elements, suggesting that nonallelic homologous recombination between these LCRs is the most probable mechanism mediating this microdeletion in COLEC11. The mutated alleles segregated with the disorder in the family and the mutation was not found in 286 northern European control chromosomes.
Carnevale, F., Krajewska, G., Fischetto, R., Greco, M. G., Bonvino, A. Ptosis of eyelids, strabismus, diastasis recti, hip defect, cryptorchidism, and developmental delay in two sibs. Am. J. Med. Genet. 33: 186-189, 1989. [PubMed: 2569826] [Full Text: https://doi.org/10.1002/ajmg.1320330210]
Keshi, H., Sakamoto, T., Kawai, T., Ohtani, K., Katoh, T., Jang, S.-J., Motomura, W., Yoshizaki, T., Fukuda, M., Koyama, S., Fukuzawa, J., Fukuoh, A., Yoshida, I., Suzuki, Y., Wakamiya, N. Identification and characterization of a novel human collectin CL-K1. Microbiol. Immunol. 50: 1001-1013, 2006. [PubMed: 17179669] [Full Text: https://doi.org/10.1111/j.1348-0421.2006.tb03868.x]
Mingarelli, R., Castriota Scanderbeg, A., Dallapiccola, B. Two sisters with a syndrome of ocular, skeletal, and abdominal abnormalities (OSA syndrome). J. Med. Genet. 33: 884-886, 1996. [PubMed: 8933348] [Full Text: https://doi.org/10.1136/jmg.33.10.884]
Rooryck, C., Diaz-Font, A., Osborn, D. P. S., Chabchoub, E., Hernandez-Hernandez, V., Shamseldin, H., Kenny, J., Waters, A., Jenkins, D., Al Kaissi, A., Leal, G. F., Dallapiccola, B., and 9 others. Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome. Nature Genet. 43: 197-203, 2011. [PubMed: 21258343] [Full Text: https://doi.org/10.1038/ng.757]